The mouse uterus has provided a system for the study of estrogen since it contains estrogens receptors and depends on estrogen stimulation for action of physiological functions. We have previously purified an estrogen-induced secretory protein from mouse uterine luminal fluid by CM-Affi-Gel Blue and reversed phase high performance liquid chromatography. The protein was found to be a approximately 70 kDa peptide existing as a single chain polypeptide under native conditions with a pI greater than or equal to 9.5. Further analysis of the protein revealed that it is glycosylated with a single N-asparagyl linkage and the N-terminus blocked to Edman degradation. The protein was not induced by testosterone or progesterone in mouse uterus. Antibody to this estrogen inducible mouse uterine protein has been used to isolate cDNA to the messenger RNA. Analysis of the deduced primary structure and additional biochemical characterization indicates that the protein is lactotransferrin. An increase in the level of lactotransferrin mRNA of at least 300-fold can be induced in the mouse uterus by estrogen. In contrast, the mRNA is virtually undetectable in rat uterine tissue following estrogen administration. The estrogenic stimulation in mouse uterus contrasts with the known prolactin dependence in mammary gland. We have mapped lactotransferrin gene to human chromosome 3 (q21-q23) and mouse chromosome 9. In future work we hope to gain some understanding of the factors leading to lactotransferrin secretion by two tissues, uterus and mammary gland, in response to different hormonal signals and, in addition, compare the structure and function of lactotransferrin gene to that of related transferrin genes that have been identified.